Pinch flow regulator

ABSTRACT

A valve for regulating fluid flow includes a housing base defining a lower cavity and comprising a pinch structure within the lower cavity, a gas inlet providing external access to the lower cavity, a base fluid inlet, and a base fluid outlet. A housing cover defines an upper cavity and comprises a cover fluid inlet and a cover fluid outlet. The cover fluid inlet is in fluidic communication with the base fluid outlet between the upper cavity and the lower cavity, and the cover fluid outlet provides external access from the upper cavity. A diaphragm is disposed between the housing base and the housing cover. A pinch plate is disposed in the lower cavity and comprises a pinch point disposed opposite the pinch structure. A pinch tube is in fluidic communication between the base fluid inlet and the base fluid outlet in the lower cavity.

CROSS-REFERENCE TO RELATED APPLICATION(S)

This application is a divisional of U.S. application Ser. No. 15/162,876filed May 24, 2016, which is a continuation of U.S. application Ser. No.14/740,573 filed Jun. 16, 2015 (now U.S. Pat. No. 9,375,716), whichclaims benefit of U.S. Provisional Application No. 62/013,471 filed Jun.17, 2014, which are incorporated herein by reference in their entirety.

TECHNICAL FIELD

This application relates to the field of fluidic flow control, and inparticular, to pinch valve regulators.

BACKGROUND

Conventional valves have been used to regulate fluid pressure and flowin different applications. In some applications, a lengthy tube having asmall inner diameter have been used to regulate fluid pressure, such asin fluidic systems that direct flow of reagents through a flow cellcontaining a sensor array. Long tubes and multiple valves haveconventionally been employed in these systems to discard reagents afterexiting a flow cell and sensor array. However, as the length of a tubeincreases, so does the possibility of clogs within the tube, as well asthe cost to manufacture a lengthy tube having a desired precision. Inaddition, variance in the inner diameter of such tubes leads to reducedaccuracy when controlling fluid flow and leads to difficulty incalibrating fluid flow systems. In view of the above, it would beadvantageous to have a device for regulating fluid flow which overcamethe deficiencies of current approaches.

SUMMARY

Methods and devices for controlling fluid flow, such as methods anddevices for generating a fixed flow rate having a linear response to acontrol gas pressure, are described. In various implementations, themethods or devices may be used in a chemical or biological system, forexample, including a sensor in fluidic communication to provide preciseand consistent fluid flow to provide fluid flows in and out of thesensor. The methods or devices are exemplified in a number ofimplementations, some of which are summarized below and throughout thespecification.

BRIEF DESCRIPTION OF THE DRAWINGS

In order to understand the invention and to see how it may be carriedout in practice, implementations will now be described, by way ofnon-limiting example only, with reference to the accompanying drawings,in which:

FIG. 1 is an exploded schematic view describing an example valve.

FIG. 2 is a cross-sectional schematic view describing an example valve.

FIG. 3A is a cross-sectional schematic view describing an example valve.

FIG. 3B is a cross-sectional schematic view describing an example valve.

FIG. 4 is a schematic view describing an example valve.

FIG. 5 is an exploded schematic view describing an example valve.

FIG. 6 is an exploded schematic view describing an example valve.

FIG. 7A is an exploded schematic view describing an example valve.

FIG. 7B is a perspective view describing an example assembled valve.

FIG. 7C is a perspective view describing an example fluid path.

FIG. 7D is a detailed perspective view describing an example fluid path.

FIG. 7E is a plan view describing an example valve.

FIG. 8A is a perspective view describing an example assembled valve.

FIG. 8B is a plan view describing an example fluid path.

FIG. 8C is a perspective view describing an example fluid path.

FIG. 8D is a perspective view describing an example fluid path cover.

FIG. 8E is a cross-sectional view describing an example assembledhousing cover.

FIG. 9 is a graph describing performance of an example valve.

FIG. 10 is a block diagram describing an example system.

DETAILED DESCRIPTION

Reference will now be made in detail to implementations, examples ofwhich are illustrated in the accompanying drawings. In the followingdetailed description, numerous specific details are set forth in orderto provide a sufficient understanding of the subject matter presentedherein. But it will be apparent to one of ordinary skill in the art thatthe subject matter may be practiced without these specific details.Moreover, the particular implementations described herein are providedby way of example and should not be used to limit the scope of theinvention to these particular implementations. In other instances,well-known structures and components have not been described in detailso as not to unnecessarily obscure aspects of the implementations of theinvention.

A system includes a pinch valve regulator for controlling reagent flowwithin the system. In particular, the pinch valve regulator can provideregulated flow at low flow rates and finds particular use in regulatingeffluent flow rates. Alternatively, the pinch valve regulator can bedisposed within an inlet flow or in the path of other fluid flows withinthe system. Such regulated low flow rates are particularly useful inchemical and biological systems utilizing expensive reagents. Forexample, the pinch valve regulator can find use in biological systemsincorporating nucleotide reagent solutions, such as systems foramplification (e.g., polymerase chain reaction (PCR) or recombinasepolymerase amplification (RPA)), sequencing, synthesis, or combinationsthereof. In particular, such pinch valve regulators have use inregulating the flow of reagents including one or more types ofnucleotides or analogs thereof. Such reagents can be used, for example,in sequencing by synthesis.

FIG. 1 provides an exploded schematic view of an example pinch valveregulator 100. The valve 100 includes a housing base 110 and a housingcover 120 disposed above the base 110. A diaphragm 130 is disposedbetween the housing base 110 and the housing cover 120. A pinch plate140 is disposed between the diaphragm 130 and the base 110. Inoperation, the pinch plate 140 moves relative to the housing base 110 topinch a pinch tube 150 against a pinch structure (as illustrated moreclearly in FIGS. 2, 3A and 3B) to restrict fluid flow through the pinchtube 150. One or more gaskets 160, 170 can be disposed between thehousing base 110 and housing cover 120 to prevent fluid leakage and toensure smooth valve operation.

FIG. 2 provides a cross-sectional schematic view of an example pinchvalve regulator. A valve 200 includes a housing base 210 and a housingcover 220 disposed over of the base 210. The housing base 210 includes alower cavity 212 and a pinch structure 214 protruding within the lowercavity 212. The housing base 210 includes a gas inlet 230, providingexternal access to the lower cavity 212. A base fluid inlet 232 providesan external access path that is connected to one end of a pinch tube 240within the lower cavity 212. The other end of a pinch tube 240 isconnected to a base fluid outlet 234. Accordingly, the pinch tube 240provides fluidic communication between the base fluid inlet 232 and thebase fluid outlet 234. The pinch tube 240 extends between the pinchstructure 214 and a pinch point 252 of a pinch plate 250.

In an example, the pinch structure 214 includes a rectangular prismextending into the lower cavity 212. As illustrated, the rectangularprism as a rounded top. In another example, the rectangular prism canhave a flat top. Alternatively, the prism can have a pointed structure,such as a triangular prims. In general, the pinch structure 214 forms acounter structure to which the pinch point 252 can secure and punch thepinch tube 240.

The base fluid outlet 234 is in turn connected to and provides fluidiccommunication with a cover fluid inlet 236 between the upper cavity andthe lower cavity to provide a fluid path through the housing base 210and the housing cover 220. The cover fluid inlet 236 is in fluidiccommunication with a cover fluid outlet 238 via a fluid path 270. Thecover fluid outlet 238 provides external access to the fluid path 270from the housing cover 220. A diaphragm 260 is disposed between thehousing base 210 and the housing cover 220 to fluidically separate thelower cavity 212 from an upper cavity 222 defined between the cover 220and the diaphragm 260.

The housing cover 220 defines an upper cavity 222 where the fluid path270 is disposed. Optionally a gasket 280 can define part of the lowercavity 212 or part of the upper cavity 222. The pinch plate 250 can bedisposed within the cavity region defined by the housing cover 220 orthe gasket 280. The base fluid outlet 234 and the cover fluid inlet 236are in fluidic communication through the gasket 280 and diaphragm 260.Alternatively, the base fluid outlet 234 and the cover fluid inlet 236can be fluidically connected external to the housing base 210 or thehousing cover 220. The diaphragm 260 provides separation between thelower cavity 212 and the upper cavity 222. A pinch plate 250 is disposedwithin the cavities 212, 222 defined within the housing cover 220 andthe housing base 210. The pinch plate 250 includes a pinch point 252that is disposed opposite the pinch structure 214. The pinch point 252is illustrated with a rounded tip. Alternatively, the pinch point 252can have a sharp tip. The pinch plate 250 moves relative to the housingbase 210 to pinch the pinch tube 240 to restrict fluid flow through thepinch tube 240 based on fluid pressure within the fluid path 270 and gaspressure within the lower cavity 212.

The valves described herein operate to regulate fluid flow as a functionof gas pressure within the lower cavity. FIG. 2 illustrates a valvestructure prior to applying fluid into the valve 200 and FIGS. 3A-3Billustrate an equilibrium state of a valve where fluid flows throughvalve 300 at a flow rate based on the input gas pressure. Animplementation of the pinch valve in operation will be described belowwith reference to FIGS. 2 and 3A-3B.

Gas pressure is applied to a gas inlet 230, 330 of the valve topressurize the lower cavity 212, 312 at an input/reference gas pressure.The pressurized lower cavity applies an upward force against the pinchplate 250, 350 and diaphragm 260, 360 towards the housing cover 220,320. Fluid is applied to the base fluid inlet 332 and flows sequentiallythrough pinch tube 340, base fluid outlet 334, cover fluid inlet 336,fluid path 370, cover fluid outlet 338, and then out of the valve. Thefluid flowing through the housing cover 320 applies a downward forceagainst the diaphragm 360 and pinch plate 350 towards the housing base310. As the fluid pressure in the fluid path 370 increases relative tothe gas pressure in the lower cavity 312, the diaphragm 360 moves towardthe housing base 310 and applies downward force against the pinch plate350. In particular, the diaphragm 360 is to motivate the pinch point 352relative to the pinch structure 314 in response to a difference betweena fluid pressure in the upper cavity 322 and a gas pressure in the lowercavity 312. For instance, the diaphragm 360 is to motivate the pinchpoint 352 towards the pinch structure 314 in response to an increase inthe fluid pressure within the upper cavity 322 relative to the gaspressure in the lower cavity 312 to restrict fluid flow in the pinchtube 340.

As the pinch plate 350 moves toward the housing base 310, the pinchpoint 352 applies a downward force onto pinch tube 340 so as to pinchthe tube 340 against the pinch structure 314 and restrict fluid flow orcause a pressure drop across the punch tube 340 and in the upper cavity322 until the input gas pressure counteracts the fluid pressure in theupper cavity 322 to thereafter provide a constant fluid flow rate fromthe valve 300. FIG. 3B illustrates a valve 300 with directional arrows380 indicating the fluid flow path through the valve 300.

The pinch actuation force of the diaphragm driven pinch valve is suchthat the output fluid pressure is regulated by the input gas pressure.By setting the pressure in the lower gas cavity 312 to a known value,fluid flow and pressure exiting the housing cover 320 is controlled. Inthis manner, the valve self-regulates to reach equilibrium and canprovide a desired constant fluid flow. In summary, the output fluidpressure at the cover fluid outlet follows the input gas pressure at thegas inlet and can be independent of the fluid pressure at the base fluidinlet. These features are disclosed in greater detail with respect toFIG. 9.

In various implementations, a valve includes a resilient structure whichis in contact with and provides lateral support to a pinch plate. FIG. 4provides a cross-sectional perspective view of the valve including thehousing cover 430 with the housing base portion removed. A pinch plate400 is provided, and a resilient structure 410 is disposed within thelower cavity of the housing base. The resilient structure 410 caninclude a spring, such as a flat spring, or a die cut flat polymer ring.The resilient structure 410 can attach to at least one pair of posts 420positioned on laterally opposite sides of the pinch plate 400. Aplurality of posts can be positioned along a circumference of the pinchplate 400. The resilient structure 410 engages the at least one pair ofposts 420 to provide the lateral support, but provides limited verticalresistance. As fluid pressure from the housing cover pushes downward onthe pinch plate 400, the resilient structure 410 counters anyundesirable lateral movement of the pinch plate 400 to maintain abalanced pinch plate 400 and can prevent the pinch point from skewingrelative to the pinch structure.

FIGS. 5-8 are directed to various implementations of a housing cover ofthe valve, and in particular, the structures related to the fluid pathand the diaphragm. As fluid flows from the base fluid outlet of thehousing base and into the cover fluid inlet, the housing cover defines afluid path having a lower area open to the upper cavity. The fluid pathis in fluidic communication between the cover fluid inlet and the uppercavity and between the upper cavity and the cover fluid outlet. Fluidflows through the fluid path and out of the housing cover through thecover fluid outlet. In various implementations, fluid flow in the uppercavity of the housing cover flows through a fluid path and isdistributed over the diaphragm. Optionally, a filter, mesh, poroussheet, or perforated membrane is disposed between the fluid path and thediaphragm to prevent extrusion of the diaphragm into the fluid path andocclusion of the fluid path by the diaphragm. The filter, mesh, porousor patterned sheet, or perforated or patterned membrane can furtherassist with distributing fluid pressure across the surface area of thediaphragm, providing force on the pinch plate.

FIG. 5 provides an exploded schematic view of an example housing cover500, fluid path 510, pressure distributor 520 and diaphragm 530. Thehousing cover 500 defines a fluid path 510 in fluidic communication withthe upper cavity. In particular, the housing cover 500 defines a fluidpath 510 having a lower area open to the upper cavity. The fluid path510 of FIG. 5 extends between a cover fluid inlet 502 and a cover fluidoutlet 504. The fluid path 510 is in fluidic communication between thecover fluid inlet and the upper cavity, as well as between the uppercavity and the cover fluid outlet. As illustrated, the fluid path 510within the housing cover 500 can have a spiral configuration that allowsfluid to flow within a spiral fluid channel. Such a configurationprovides fluid flow over a larger surface area of the diaphragm 530 toprovide balanced and even downward pressure to a pinch plate.Alternatively, the fluid path can have a shape other than a spiralshape, and can have any configuration that provides fluid flow over thediaphragm 530. For example, the fluid path can provide a set ofchannels, such as straight channels, wavy channels, concentric circles,or any combination thereof.

As illustrated in FIG. 5, fluid enters the fluid path 510 from the coverfluid inlet 502 along the perimeter and exits the cover fluid outlet 504at a position over the location where the pinch point and pinchstructure pinches the pinch tube. The pressure distributor 520 can bedisposed in the upper cavity of the housing cover 500 between the fluidpath 510 and the diaphragm 530 to further distribute fluid flow from thefluid path 510 over the diaphragm 530 and limit encroachment of thediaphragm 530 into the fluid path 510. As fluid flow initially travelsthrough the spiral fluid path, before the diaphragm 530 is pushed down,the pressure distributor 520 allows fluid to spread across the diaphragm530.

The pressure distributor 520 can be a filter, such as a sintered metalfilter or a sintered ceramic frit, or can be a mesh structure, such as awire or polymer mesh. The filter or mesh can include pores or small openareas on its surface allowing fluid flowing through fluid path 510 toseep out from the fluid path 510 and flow over substantially the entiresurface area of the pressure distributor 520 and diaphragm 530, asopposed to just the fluid path 510. While much of the fluid in the fluidpath 510 stays within the spiral channel, fluid will spread out over thefilter or mesh via the pores or openings to distribute fluid pressure.In an example, the filter or mesh provides further consistency inproviding downward pressure on the diaphragm 530 and pinch plate. Inaddition or alternatively, the filter or mesh can prevent extrusion ofthe diaphragm into the fluid path that would limit fluid flow within thefluid path, particularly when initially starting fluid flow.

FIG. 6 provides an exploded schematic view of an example housing cover600, fluid path 610, pressure distributor 620 and diaphragm 630. Thefluid path 610 of FIG. 6 extends from the cover fluid inlet 602 to thecover fluid outlet 604. The fluid path 610 has a spiral-likeconfiguration that provides fluid flow over a large surface area of thediaphragm 630 to provide balanced or even downward pressure to a pinchplate. A pressure distributor 620 can be disposed in the upper cavity ofthe housing cover 600 between the fluid path 610 and the diaphragm 630to further distribute fluid flow over the diaphragm 630. In particular,the pressure distributor 620 can prevent the diaphragm 630 fromencroaching into the fluid path 610 and limiting fluid flow within thefluid path 610.

In FIG. 6, the pressure distributor 620 is a membrane disposed betweenthe diaphragm 630 and the fluid path 610. The membrane includes aplurality of small holes or openings 622 underneath the channels of thefluid path 610. For example, the fluid path 610 in FIG. 6 has a spiralconfiguration that forms concentric circles. Accordingly, the membrane620 includes a plurality of small holes 622 forming concentric circlescorresponding to the spiral fluid path 610. In other examples, themembrane 620 can include a plurality of small holes following thepattern of the fluid path 610, such as spiral configurations, concentriccircles, straight lines, wavy lines, a regular or irregular array, orany combination thereof. The membrane 620 with small holes 622 allowsfluid flowing through fluid path 610 to seep out from the fluid path 610and flow over substantially the entire surface area of the pressuredistributor 620 and diaphragm 630, as opposed to just the fluid path610. While most of the fluid in the fluid path 610 stays within thespiral channel, some fluid spreads out over the diaphragm 630 via theholes 622 to distribute fluid pressure. The use of a membrane 620provides further consistency in providing downward pressure on thediaphragm 630 and a pinch plate.

The housing cover 600 can include a plurality of fasteners 608 forassembly with corresponding fastener holes in a housing base to fastenthe housing cover to the housing base. The edges of the pressuredistributor 620 can be scalloped or have projections 624 correspondingto the shape of the fastener 608 for aligned seating of the distributor620 and prevent rotation. The fluid path and diaphragm can also definescalloped projections.

In various implementations, the membrane 620 includes a sheet having athickness in a range of 0.005 inches to 0.5 inches, such asapproximately 0.01 inches, with holes having an average diameter in arange of 0.001 inches to 0.01 inches, such as approximately 0.006inches. The pressure distributor 620 can be machined or die cut for easeof manufacture and reduction of cost.

FIG. 7A provides an exploded schematic view of an example housing cover700, fluid path 710, pressure distributor 720 and diaphragm 730. Thepressure distributor 720 is disposed between fluid path 710 anddiaphragm 730. Fluid flow through the fluid path 710 is distributed bythe pressure distributor 720 over a large surface area of the diaphragm730 to provide a balanced downward pressure on the diaphragm 730 and apinch plate 740. The configurations described below allow the fluid path710 and the pressure distributor 720 to be machined or die cut for easeof manufacture and reduction of cost.

FIG. 7B is a bottom perspective view describing an example assembledvalve. The fluid path 710 extends from the cover fluid inlet 702 to thecover fluid outlet 704. The fluid path 710 defines a lateral channel 712and circular channels 714 along an outer perimeter. At the center of thefluid path 710, the lateral channel 712 opens up to provide fluid flowinto and around an inner island 716. The inner island 716 defines a setof grooves or vertical channels 717. Fluid flows from the grooves orvertical channels 717 of the inner island 716 past the pressuredistributor 720 to distribute fluid over the diaphragm 730. Likewise,the circular channel 714 defines a set of grooved vertical channels 718along the outer edges of the fluid path 710. The pressure distributor720 is disposed over the circular channels 714, but allows fluidiccommunication between the fluid path 710 and the diaphragm 730 via thevertical channels 718.

Together, the fluid path 710 and pressure distributor 720 provide fluidflow over a large surface area of the diaphragm 730 to provide balancedor even downward pressure to a pinch plate or prevent the diaphragm 730from encroaching into the fluid path 710. The pressure distributor 720can also define projections 719 that fit around corresponding fasteners706 to ensure proper seating and prevent rotation.

FIG. 7C is a bottom perspective view describing an example fluid path.In particular, an underside of the fluid path 710 is illustrated andincludes the cover fluid inlet 702, the cover fluid outlet 704, lateralchannel 712, circular channels 714, inner island 716, and verticalchannels 717, 718. As fluid pressure increases in the fluid path 710,transient pressure differences between the fluid flow within thechannels 712, 714 and fluid adjacent the diaphragm causes fluid to movethrough the vertical channels 717, 718 and onto the diaphragm, providinga downward force on the diaphragm. When fluid flow into the valve isstopped, the upward pressure on the diaphragm pushes the fluid back intothe channels 712, 714 via the vertical channels 717, 718, respectively.The housing cover 700 can include a plurality of recesses 715 into whichthe pressure distributor (e.g., the pressure distributor 720 of FIG. 7Aand FIG. 7B) can fit to hold the filter in place.

FIG. 7D is a detailed perspective view describing an example fluid path.The vertical channels 717, 718 are illustrated and show the pressuredistributor 720 is disposed over portions of the channels 717, 718 andcan allow fluid to distribute over the diaphragm (illustrated in FIG.7A). The channels 712, 714 are covered by the pressure distributor 720.

FIG. 7E is a bottom plan view of the housing cover 700 from theperspective of the housing base. As discussed above, the pressuredistributor 720 is disposed over the lateral channel and circularchannels such that fluid can flow out from the channels and onto thediaphragm, and the diaphragm does not encroach into the fluid path. Thevertical channels 717, 718 are only partially covered by the pressuredistributor 720 to allow fluid to distribute over the diaphragm(illustrated in FIG. 7A). As such, the pressure distributor 720 isdisposed over the circular channel 714 and the lateral channel 712(illustrated in FIG. 7B) and allows fluidic communication between thefluid path and the pressure distributor where the pressure distributoris disposed over a portion of the circular channel and the lateralchannel. The pressure distributor 720 can also define projections 722that are shaped corresponding to fasteners 706 to ensure proper seatingand prevent rotation.

FIG. 8A is a top perspective view describing an example assembled valveincluding a housing cover 800, fluid path 810, and fluid path cover 820.The housing cover 800 is provided above a housing base and directlyabove a diaphragm without an intervening pressure distributor, such as amembrane or filter described above. The housing cover 800 includes afluid path 810 that extends from a cover fluid inlet 802 to a coverfluid outlet 804. The fluid path 810 can have a spiral configurationthat allows fluid to flow within a spiral fluid channel. Thisconfiguration provides fluid flow over a larger surface area of adiaphragm to provide balanced and even downward pressure to a pinchplate (not shown). The fluid path can have a shaper other than a spiralshape, and can have any configuration that provides fluid flow evenlyover the diaphragm. The housing cover 800 defines a fluid path 810 influidic communication via openings or holes 812 with the upper cavityand is disposed opposite the upper cavity. While illustrated as circularholes, the openings can be circular, or can be slits, or alternativelycan have a mesh pattern, or any combination thereof.

A fluid path cover 820 is placed over to cover the fluid path 810 toprevent fluid from seeping out above the channels of the fluid path 810.A gasket 814 can be provided as an additional barrier to prevent fluidfrom leaking out of the housing cover 800 and disposed between the fluidpath cover 820 and the fluid path 810. The fluid path 810 includes aplurality of openings or holes 812 throughout the length of the fluidpath 810 that are in fluidic communication between the fluid path andthe diaphragm below housing cover 800. The holes 812 can be machined ordie cut.

The housing cover 800 can include a plurality of fasteners 806 forassembly with corresponding fastener holes in a housing base and ahousing cover. The edges of the fluid path cover 820 can be formed toinclude recesses 822 corresponding to the fasteners to engage the fluidpath cover 820 with the housing cover 800 and prevent rotation.

FIG. 8B is a top plan view describing an example housing cover 800 andfluid path 810 with the fluid path cover removed. The housing cover 800includes a fluid path 810 that extends from a cover fluid inlet 802 to acover fluid outlet 804 and includes a plurality of holes 812 throughoutthe length of the fluid path 810 that allow fluid to flow between thechannel and the diaphragm below housing cover 800. A gasket 814 can beprovided to enclose the fluid path 810 and prevent fluid from leakingout of the housing cover 800. A plurality of fasteners 806 can fit intocorresponding fastener holes 807 (illustrated in FIG. 8C) in the housingcover 800 and can also secure the gasket 814 to the housing cover 800.

FIG. 8C is a top perspective view of the housing cover 800 illustratedin FIG. 8B with the fasteners and gasket removed. A set of fastenerholes 807 are provided for corresponding fasteners 806 (illustrated inFIG. 8B) to secure the housing cover 800 to a housing base. A gasket 814can be secured in a gasket recess 815 of the housing cover 800. Coverfluid inlet 802, cover fluid outlet 804, fluid path 810 and holes 812can be similar to those discussed above in FIGS. 8A-8B.

FIG. 8D is a perspective view describing an example fluid path cover820. The fluid path cover 820 is shaped to fit over the housing cover800 (illustrated in FIG. 8C) and prevent fluid from leaking out of thetop of the fluid path 810 (illustrated in FIG. 8C). In FIG. 8D, thefluid path cover 820 can be secured to the housing cover 800 by recesses822 corresponding to the shape of a fastener 806 to secure the fluidpath cover 820 to the housing cover 800 (illustrated in FIG. 8C).

FIG. 8E is a cross-sectional view describing an example assembledhousing cover 800 and fluid path cover 820. The fluid path cover 820 issecured above the housing cover 800 such that fluid does not spill outfrom above the fluid path 810. Instead, fluid flows in and out of thefluid path 810 via the holes 812. The fluid that is within the fluidpath 810 is further contained by the gasket 814. Cover fluid inlet 802,cover fluid outlet 804, fluid path 810 and holes 812 can be similar tothose discussed above in FIGS. 8A-8B.

In an exemplary application, a fluid flow system can be calibrated usingthe pinch valve regulator. Calibration of the valve in a fluid flowsystem provides an understanding of the behavior of the valve relativeto the resistance of the system coupled therewith. Fluid resistancewithin the system can cause pressure drop, particularly throughrestrictive structures, such as valves and restrictors downstream fromthe pinch valve regulator. In an example, the downstream fluidresistance can be determined using the pinch valve regulator. Forexample, with reference to FIG. 3A and FIG. 3B, a wash solution issupplied to the base fluid inlet 332 at a measured pressure (e.g.,approximately 12 psi) and a reference gas pressure is supplied to thegas inlet 330, for example, at a measured gas pressure (e.g.,approximately 1-2 psi). The fluid path of the diaphragm 360 fills withan equilibrium wash solution volume and a flow rate (e.g., approximately40 μL/s) is output from the valve 300.

When an upstream fluid valve is closed and the reference gas pressureline is isolated from a gas pressure source, the gas pressure in thelower cavity 312 drives the wash solution volume in the upper cavityabove the diaphragm 360 and in the fluid path 370 out of the pinch valveregulator through the cover fluid outlet 338. The volume of thereference gas increases to displace the wash volume leaving the valve.

With the upstream fluid valve closed and the reference gas pressure lineisolated from the gas inlet 330, the gas pressure can be determined froma pressure sensor on the reference gas pressure line (not shown). Gasexpansion in the lower cavity within the housing base leads to a smallpressure decay on the gas pressure, for example, consistent with idealgas law behavior where the product of pressure and volume is conserved.With knowledge of the absolute atmospheric pressure and total initialvolume of the lower cavity and reference gas line, a pressure decaycurve allows computation of resistance, and hence the flow rate of thewash volume during normal operation.

Another method of calibrating a fluid flow system using the pinch valveregulator is described below. The wash solution is supplied to the basefluid inlet 332 from a pressurized chamber (not shown) having aheadspace that drives the wash solution out of the chamber and throughthe valve. A reference gas pressure is supplied to the gas inlet 330 andthe headspace is pressurized at a set pressure. The initial volume andpressure of the headspace of the chamber is measured. The chamber isisolated from the pressure source, while maintaining the reference gaspressure in the lower cavity of the valve. Thereafter, the headspaceincreases in volume and reduces in pressure as the wash solution isdriven from the chamber. A final pressure of the chamber is measured andthe final volume can be estimated. The initial and final volumes andpressures are used to determine the resistance. During operation, theflow rate of the fluid can be determined using the resistance.

The valve thus can provide accurate and precise control of pressure thatcan be measured and calibrated with direct use of the valve. Diagnosticsand calibration can be performed by operating the valve.

FIG. 9 is a graph illustrating the performance of an example valve. FIG.9 illustrates the relationship between the reference gas pressure (Pref)against the output liquid pressure (Pout) for a set of different inputliquid pressures (Psource). The linear behavior is illustrated where theoutput liquid pressure responds linearly to the reference gas pressurewhen the reference gas pressure is in a range of 0% to 90% of the inputliquid pressure.

Exemplary pinch valve regulators are useful in chemical or biologicalprocesses where reagents are delivered to one or more reactors orreaction sites. The reaction sites can be monitored by chemical,electrical or optical sensors. Exemplary systems include methods andapparatuses for carrying out DNA sequencing, and in particular, pH-basedDNA sequencing. For example, in pH-based DNA sequencing, baseincorporations are determined by measuring hydrogen ions that aregenerated as natural byproducts of polymerase-catalyzed extensionreactions. DNA templates each having a primer and polymerase operablybound are loaded into reaction chambers or microwells, after whichrepeated cycles of deoxynucleoside triphosphate (dNTP) addition andwashing are carried out. Such templates are typically attached as clonalpopulations to a solid support, such as a microparticle, bead, or thelike, and such clonal populations are loaded into reaction chambers. Ineach addition step of the cycle, the polymerase extends the primer byincorporating added dNTP when the next base in the template is thecomplement of the added dNTP. If there is one complementary base, thereis one incorporation, if two, there are two incorporations, if three,there are three incorporations, and so on. With each such incorporationthere is a hydrogen ion released, and collectively a population oftemplates releasing hydrogen ions causing very slight changes to thelocal pH of the reaction chamber which is detected by an electronicsensor. In addition to sequencing, the device herein can be useful forother biological instruments that require fluid storage or delivery.

FIG. 10 diagrammatically illustrates a system employing a valve, forexample, for carrying out pH-based nucleic acid sequencing. Eachelectronic sensor of the apparatus generates an output signal thatdepends on the value of a reference voltage. The fluid circuit permitsmultiple reagents to be delivered to the reaction chambers.

In FIG. 10, system 1000 containing fluidics circuit 1002 is connected byinlets to at least two reagent reservoirs 1014, to waste reservoir 1020,and to biosensor 1034 by fluid pathway 1032 that connects fluidics node1030 to inlet 1038 of biosensor 1034 for fluidic communication. Reagentsfrom reservoirs 1014 can be driven to fluidic circuit 1002 by a varietyof methods including pressure, pumps, such as syringe pumps, gravityfeed and the like, and are selected by control of valves 1050. Reagentsfrom the fluidics circuit 1002 can be driven through the pinch valve1042 receiving signals from control system 1018 to waste container 1020.Reagents from the fluidics circuit 1002 can also be driven through thepinch valve 1044 receiving signals from the control system 1018 to thewaste container 1036. Control system 1018 includes controllers forvalves 1050, and pinch valves 1042, 1044, that generate signals foropening and closing via electrical connection 1016.

Control system 1018 also includes controllers for other components ofthe system, such as wash solution valve 1024 connected thereto byelectrical connection 1022, and reference electrode 1028. Control system1018 can also include control and data acquisition functions forbiosensor 1034. In one mode of operation, fluidic circuit 1002 deliversa sequence of selected reagents 1, 2, 3, 4, or 5 to biosensor 1034 underprogrammed control of control system 1018, such that in between selectedreagent flows, fluidics circuit 1002 is primed and washed, and biosensor1034 is washed. Fluids entering biosensor 1034 exit through outlet 1040and are deposited in waste container 1036 via control of pinch valveregulator 1044. The valve 1044 is in fluidic communication with thesensor fluid output 1040 of the biosensor 1034.

The housing components can be constructed from a variety of materials,including metals, glass, ceramics, polymers, or the like. In an example,the material can be a transparent material, such as polycarbonate,polymethyl methacrylate, or the like.

As mentioned above, fluidic circuits can be fabrication by a variety ofmethods and materials. Factors to be considered in selecting materialsinclude degree of chemical inertness required, operating conditions,e.g. temperature, and the like, volume of reagents to be delivered,whether or not a reference voltage is required, manufacturability, andthe like. For meso-scale and larger scale fluid deliveries, conventionalmilling techniques can be used to fabricate parts that can be assembledinto fluidic circuits. In one aspect, plastics such as polycarbonate,polymethyl methacrylate, and the like, can be used to fabricate fluidicscircuits.

In one aspect, a valve includes a housing base defining a lower cavity,with the housing base including a pinch structure within the lowercavity, a gas inlet providing external access to the lower cavity, abase fluid inlet, and a base fluid outlet. A housing cover defines anupper cavity and includes a cover fluid inlet and a cover fluid outlet.The cover fluid inlet is in fluidic communication with the base fluidoutlet between the upper cavity and the lower cavity. The cover fluidoutlet provides external access from the upper cavity. A diaphragm isdisposed between the housing base and the housing cover and fluidicallyseparates the lower cavity from the upper cavity. A pinch plate isdisposed in the lower cavity and includes a pinch point disposedopposite the pinch structure. A pinch tube is provided in fluidiccommunication between the base fluid inlet and the base fluid outlet inthe louver cavity, where the pinch tube extends between the pinchstructure and the pinch point.

In a related aspect, the diaphragm is to motivate the pinch pointrelative to the pinch structure in response to a difference between afluid pressure in the upper cavity and a gas pressure in the lowercavity. For instance, the diaphragm is to motivate the pinch pointtoward the pinch structure in response to an increase in the fluidpressure within the upper cavity relative to the gas pressure in thelower cavity to restrict fluid flow in the pinch tube.

In a related aspect, a resilient structure is in contact with andprovides lateral support the pinch plate. The resilient structure caninclude a spring. The pinch plate can include at least one pair of postspositioned on laterally opposite sides of the pinch plate, where theresilient structure engages the at least one pair of posts to providethe lateral support.

In a related aspect, the housing cover further defines a fluid path influidic communication with the upper cavity. The housing cover candefine a fluid path having a spiral configuration extending from thecover fluid inlet and the cover fluid outlet. The housing cover candefine a fluid path in fluidic communication between the cover fluidinlet and the upper cavity. The housing cover can define a fluid path influidic communication between the upper cavity and the cover fluidoutlet. The housing cover can define a fluid path having a lower areaopen to the upper cavity.

In a related aspect, a pressure distributor is disposed in the uppercavity. The pressure distributor can include a filter. The filter caninclude a sintered metal filter. The pressure distributor can include adistributor plate. The distributor plate further defines a plurality ofopenings corresponding to the fluid path. A gasket can be disposedbetween the housing base and the housing cover. The base fluid outletand the cover fluid inlet can be in in fluidic communication through thegasket. The base fluid outlet and the cover fluid inlet can be influidic communication through the diaphragm.

In another aspect, the housing cover includes a fastener fastening thehousing cover to the housing base. A pressure distributor defines aprojection corresponding to a shape of the fastener. The fluid pathdefines a lateral channel and a circular channel. The circular channeldefines a plurality of grooved vertical channels. The lateral channeldefines an inner island. The inner island defines a plurality of groovedvertical channels. The pressure distributor can be disposed in the uppercavity and disposed over the circular channel and the lateral channeland allow fluidic communication between the fluid path and the pressuredistributor. The pressure distributor can be disposed over a portion ofthe circular channel and the lateral channel.

In another aspect, the fluid path can define a recess to hold a pressuredistributor. A pressure distributor can prevent the diaphragm fromencroaching into the fluid path. The housing cover can further define afluid path in fluidic communication with the upper cavity and disposedopposite the upper cavity. The fluid path can further define a pluralityof openings, wherein the fluid path and the diaphragm are in fluidiccommunication through the plurality of openings. A fluid path cover canbe provided to cover the fluid path. A gasket can be disposed betweenthe fluid path cover and the fluid path.

In another aspect, a fluid pressure at the cover fluid outlet dependslinearly on a gas pressure in the lower cavity for a first range of thegas pressure to a fluid pressure at the base fluid inlet. The firstrange is 0% to 90% of the gas pressure to the fluid pressure at the basefluid inlet.

In another aspect, a system includes at least two reservoirs, eachreservoir of the at least two reservoirs including a reagent solution. Afluid pathway is provided in fluidic communication with each of the atleast two reservoirs. A biosensor is provided including a sensor fluidinlet and a sensor fluid outlet. The sensor fluid inlet of the biosensoris in fluidic communication with the fluid pathway. A valve is providedin fluidic communication with the sensor fluid outlet of the biosensor.The valve includes a housing base defining a lower cavity and thehousing base including a pinch structure within the lower cavity, a gasinlet providing external access to the lower cavity, a base fluid inlet,and a base fluid outlet. A housing cover defines an upper cavity andincludes a cover fluid inlet and a cover fluid outlet. The cover fluidinlet is in fluidic communication with the base fluid outlet between theupper cavity and the lower cavity. The cover fluid outlet providesexternal access from the upper cavity. A diaphragm is disposed betweenthe housing base and the housing cover and fluidically separates thelower cavity from the upper cavity. A pinch plate is disposed in thelower cavity and includes a pinch point disposed opposite the pinchstructure. A pinch tube is provided in fluidic communication between thebase fluid inlet and the base fluid outlet in the lower cavity, wherethe pinch tube extends between the pinch structure and the pinch point.

In another aspect, a method of controlling fluid flow includes applyinggas pressure to a gas inlet of a valve. The valve includes a housingbase defining a lower cavity and comprising a pinch structure within thelower cavity, a gas inlet providing external access to the lower cavity,a base fluid inlet, and a base fluid outlet. A housing cover defines anupper cavity and includes a cover fluid inlet and a cover fluid outlet.The cover fluid inlet is in fluidic communication with the base fluidoutlet between the upper cavity and the lower cavity. The cover fluidoutlet provides external access from the upper cavity. A diaphragm isdisposed between the housing base and the housing cover and fluidicallyseparates the lower cavity from the upper cavity. A pinch plate isdisposed in the lower cavity and includes a pinch point disposedopposite the pinch structure. A pinch tube is provided in fluidiccommunication between the base fluid inlet and the base fluid outlet inthe lower cavity, where the pinch tube extends between the pinchstructure and the pinch point. A fluid is applied to the base fluidinlet.

In a related aspect, a method of calibrating fluid flow in a valveincludes measuring the pressure of the fluid applied to the base fluidinlet and the gas pressure applied to the gas inlet of the valve. Asecond valve provided upstream of the cover fluid outlet of the valve isclosed. A gas pressure source applying the gas pressure is isolated fromthe gas pressure applied to the gas inlet. The isolated applied gaspressure in the lower cavity is measured. A resistance of a systemcoupled to the valve is determined based on the measured isolatedapplied gas pressure and an initial volume of the lower cavity. Duringoperation, fluid flow rates can be determined based on the determinedresistance of the valve.

In another related aspect, a method of calibrating fluid flow in a valveincludes measuring a first headspace volume of a pressurized chambercoupled to the base fluid inlet, the pressure of the fluid applied tothe base fluid inlet, and the gas pressure applied to the gas inlet ofthe valve. Pressurization to the chamber is turned off and a secondpressure of the chamber and a second headspace volume is measured. Aresistance of a system coupled to the valve is determined based on themeasured first headspace volume, the second headspace volume, the fluidpressure and the second pressure. A fluid flow rate is determined basedon the determined resistance of the system.

Features of the above aspects can be interchanged in embodimentsenvisaged herein.

The practice of the present invention may employ, unless otherwiseindicated, conventional techniques and descriptions of mechanicalengineering, electronics, fluid mechanics, and materials science, whichare within the skill of the art. Such conventional techniques include,but are not limited to, design and fabrication of fluidics andmicrofluidics devices, and the like. Specific illustrations of suitabletechniques can be had by reference to the example herein below. However,other equivalent conventional procedures may, of course, also be used.

The methods and devices are particularly well suited for meso-scale andmicro-scale systems, for example, systems having passage cross-sectionsin the range of tens of square microns to a few square millimeters, orhaving flow rates in the range of from a few nL/sec to a hundreds ofμL/sec. In an embodiment, a pinch valve regulator can be used toregulate flow of reagents, particularly at low flow rates, such as flowrates in the range of from 100 μL/min to 5.0 mL/min. In a particularexample, such a pinch vale regulators can regulate the flow of reagentsat a flow rate in a range of 0.2 mL/min to 4.0 mL/min, such as 0.4mL/min to 3.0 mL/min. In particular, the methods and devices may bemicrofluidic devices including passages that have effective diameters ina range of 0.1 micrometers to 500 micrometers.

Note that not all of the activities described above in the generaldescription or the examples are required, that a portion of a specificactivity may not be required, and that one or more further activitiesmay be performed in addition to those described. Still further, theorder in which activities are listed are not necessarily the order inwhich they are performed.

In the foregoing specification, the concepts have been described withreference to specific embodiments. However, one of ordinary skill in theart appreciates that various modifications and changes can be madewithout departing from the scope of the invention as set forth in theclaims below. Accordingly, the specification and figures are to beregarded in an illustrative rather than a restrictive sense, and allsuch modifications are intended to be included within the scope ofinvention.

As used herein, the terms “comprises,” “comprising,” “includes,”“including,” “has,” “having” or any other variation thereof, areintended to cover a non-exclusive inclusion. For example, a process,method, article, or apparatus that comprises a list of features is notnecessarily limited only to those features but may include otherfeatures not expressly listed or inherent to such process, method,article, or apparatus. Further, unless expressly stated to the contrary,“or” refers to an inclusive-or and not to an exclusive-or. For example,a condition A or B is satisfied by any one of the following: A is true(or present) and B is false (or not present), A is false (or notpresent) and B is true (or present), and both A and B are true (orpresent).

Also, the use of “a” or “an” are employed to describe elements andcomponents described herein. This is done merely for convenience and togive a general sense of the scope of the invention. This descriptionshould be read to include one or at least one and the singular alsoincludes the plural unless it is obvious that it is meant otherwise.

Benefits, other advantages, and solutions to problems have beendescribed above with regard to specific embodiments. However, thebenefits, advantages, solutions to problems, and any feature(s) that maycause any benefit, advantage, or solution to occur or become morepronounced are not to be construed as a critical, required, or essentialfeature of any or all the claims.

After reading the specification, skilled artisans will appreciate thatcertain features are, for clarity, described herein in the context ofseparate embodiments, may also be provided in combination in a singleembodiment. Conversely, various features that are, for brevity,described in the context of a single embodiment, may also be providedseparately or in any subcombination. Further, references to valuesstated in ranges include each and every value within that range.

What is claimed is:
 1. A method of controlling fluid flow comprising:applying a gas pressure to a gas inlet of a valve, the valve comprising:a housing base defining a lower cavity and comprising a pinch structurewithin the lower cavity, a gas inlet providing external access to thelower cavity, a base fluid inlet, and a base fluid outlet; a housingcover defining an upper cavity; a diaphragm disposed between the housingbase and the housing cover and fluidically separating the lower cavityfrom the upper cavity; a pinch plate disposed in the lower cavity andcomprising a pinch point disposed opposite the pinch structure; and apinch tube in fluidic communication between the base fluid inlet and thebase fluid outlet in the lower cavity, the pinch tube extending betweenthe pinch structure and the pinch point, the pinch plate to adjust therelative position of the pinch point and pinch structure in response toa pressure in the upper cavity; and applying a fluid to the base fluidinlet.
 2. The method of claim 1, further comprising: measuring thepressure of the fluid applied to the base fluid inlet and the gaspressure applied to the gas inlet of the valve; closing a second valveprovided upstream of the cover fluid outlet of the valve; isolating agas pressure source applying the gas pressure from the gas pressureapplied to the gas inlet; measuring the isolated applied gas pressure inthe lower cavity; determining a resistance of a system coupled to thevalve based on the measured isolated applied gas pressure and an initialvolume of the lower cavity; and determining a fluid flow rate based onthe determined resistance of the system.
 3. The method of claim 2,further comprising: measuring a first headspace volume of a pressurizedchamber coupled to the base fluid inlet, the pressure of the fluidapplied to the base fluid inlet and the gas pressure applied to the gasinlet of the valve; turning off a pressurization to the chamber;measuring a second pressure of the chamber and a second headspacevolume; determining a resistance of a system coupled to the valve basedon the measured first headspace volume, the second headspace volume, thefluid pressure and the second pressure; and determining a fluid flowrate based on the determined resistance of the system.
 4. The method ofclaim 1, wherein the diaphragm is to motivate the pinch point relativeto the pinch structure in response to a difference between the pressurein the upper cavity and a gas pressure in the lower cavity.
 5. Themethod of claim 4, wherein the diaphragm is to motivate the pinch pointtoward the pinch structure in response to an increase in the pressurewithin the upper cavity relative to the gas pressure in the lower cavityto restrict fluid flow in the pinch tube.
 6. The method of claim 1,wherein the valve further comprises a resilient structure in contactwith and providing lateral support to the pinch plate.
 7. The method ofclaim 6, wherein the resilient structure includes a spring.
 8. Themethod of claim 7, wherein the housing cover further defines a fluidpath in fluidic communication with the upper cavity.
 9. The method ofclaim 8, wherein the fluid path defines a lateral channel and a circularchannel.
 10. The method of claim 9, wherein the circular channel definesa plurality of grooved vertical channels.
 11. The method of claim 9,wherein the lateral channel defines an inner island.
 12. The method ofclaim 11, wherein the inner island defines a plurality of groovedvertical channels.
 13. The method of claim 9, wherein the valve furthercomprises a pressure distributor disposed in the upper cavity anddisposed over the circular channel and the lateral channel and allowsfluidic communication between the fluid path and the pressuredistributor.
 14. The method of claim 13, wherein the pressuredistributor is disposed over a portion of the circular channel and thelateral channel.
 15. The method of claim 8, wherein the fluid pathdefines a recess to hold a pressure distributor.
 16. The method of claim6, wherein the pinch plate includes at least one pair of postspositioned on laterally opposite sides of the pinch plate, the resilientstructure engaging the at least one pair of posts to provide the lateralsupport.
 17. The method of claim 1, wherein the valve further comprisesa pressure distributor disposed in the upper cavity.
 18. The method ofclaim 17, wherein the pressure distributor includes a membrane disposedbetween the diaphragm and the fluid path.
 19. The method of claim 1,wherein the housing cover further defines a fluid path in fluidiccommunication with the upper cavity, the fluid path formed on a surfaceof the housing cover disposed opposite as surface of the housing coverdefining the upper cavity, wherein the fluid path further defines aplurality of openings, wherein the fluid path and the diaphragm are influidic communication through the plurality of openings, wherein thevalve further comprises a fluid path cover covering the fluid path. 20.The method of claim 1, wherein a fluid pressure at the cover fluidoutlet responds linearly on a gas pressure in the lower cavity for afirst range of the gas pressure to a fluid pressure at the base fluidinlet, wherein the first range is 0% to 90% of the gas pressure to thefluid pressure at the base fluid inlet.